1h-imidazo(4,5-b)pyridine compounds

ABSTRACT

SUBSTITUTED 3-HYDROXY-2 - (1,1 - DIFLUOROALKYL) - 1HIMIDAZO(4,5-B)PYRIDINE COMPOUNDS USEFUL AS HERBICIDES; AND INTERMEDIATES USEFUL IN THE SYNTHESIS OF THESE COMPOUNDS. IN ADDITION TO EXHIBITING HERBICIDAL ACTIVITY, THE SUBSTITUTED 1 - HYDROXY-2-(1,1-DIFLUOROALKYL)-1H-IMIDAZO(4,5-B)PYRIDINE COMPOUNDS ARE OF LOW MAMMALIAN TOXICITY.

United States Patent 7 3,813,408 1H-IMIDAZO(4,5-b)PYRIDINE COMPOUNDSGeorge 0. P. Doherty, Greenfield, Ind., and Kenneth H. Fuhr, Columbus,Ohio; said Doherty now by change of name George 0. P. ODoherty;assignors to Eli Lilly and Company, Indianapolis, Ind. No Drawing.Continuation-impart of abandoned application Ser. No. 21,535, Mar. 20,1970. This application Sept. 17, 1971, Ser. No. 181,574

Int. Cl. C07d 31/42 US. Cl. 260-496 H 8 Claims ABSTRACT OF THEDISCLOSURE Substituted l-hydroxy-Z (1,1 difluoroalkyl) 1H-imidazo(4,5-b)pyridine compounds useful as herbicides; and intermediatesuseful in the synthesis of these compounds. In addition to exhibitingherbicidal activity, the substituted 1hydroxy-2-(1,l-difluoroalkyl)-1H-imidazo- (4,5-b)pyridine compounds areof low mammalian toxicity.

CROSS-REFERENCE TO RELATED APPLICATION This is a continuation-in-part ofour copending application, Ser. No. 21,535, filed Mar. 20, 1970 andabandoned after the filing of this application.

SUMMARY OF THE INVENTION The present invention is directed tosubstituted-l-hydroxy 2-(1,l-difluoroalkyl)-1H-imidazo(4,5-b)pyridinecompounds of the following formula:

and the salts thereof. In the above and succeeding formulae throughoutthe present specification and claims, R represents hydrogen, chlorine,fluorine, difiuoromethyl, perfluoroalkyl of C -C or radical of theformula fifi. \i/i wherein each Z independently represents hydrogen orhalogen and m represents 0 or 1; R represents amino, halogen, nitro,cyano, loweralkyl of C -C perfluoroalkyl of C -C --CF Cl, CF H, orloweralkylsulfonyl of C -C and n represents an integer of from 1 to 3,both inclusive, subject to the limitations (1) that all R substitutentstogether contain not more than 8 carbon atoms; (2) that not more thantwo R symbols represents loweralkylsulfonyl groups; and (3) that wheretwo loweralkylsulfonyl groups are present, they are located at thePatented May 28, 1974 5- and 7-positions. These compounds are useful asherbicides. Hence, the present invention is also directed to methodsemploying and compositions comprising the compounds as herbicides. Theabove-described compounds are also useful as starting materials fromwhich other of the above-described compounds can be prepared.

In addition, the present invention is also directed to various separateclasses of intermediates useful in the preparation of the compoundsdefined above, including the most intermediate precursors of theformulae:

NH-o-oFr-m wherein R and R are as defined above, and

wherein R represents loweralkylsulfonyl of C C both inclusive.

DETAILED DESCRIPTION OF THE INVENTION In the present specification andclaims, the term halogen" is employed to designate bromine, chlorine,fluorine, and iodine, only.

An essential and distinguishing structural feature of the compounds ofthe present invention is the substituent at the 2 position (CF Rrepresentative such radicals include the following:

Preferred groups are trifluoromethyl, difiuoromethyl,difluorochloromethyl, 1,1,2,2-tetra fluoroethyl, and pentafluoroethyl. g

The compounds of the present'invention are typically crystalline solids.Two synthetic routes are useful in the preparation of follows:

In accordance with the foregoing reaction route, the initialsubstituted-Z-amino--3-nitropyridine compound is acylated to yield thecorresponding substituted-2-(2,2-difluoroalkanamido)-3-nitropyridine,which is then reacted further to yield the final product in accordancewith the present invention. Because of the ready availability ofsuitable starting materials, this reaction scheme is particularly suitedto the preparation of the mono-substituted compounds of the presentinvention. Where suitable starting materials are available, it isequally suited to the preparation of diand til-substituted compounds.However, the diand tri-substituted compounds are often preferablyprepared in an alternate synthetic route, discussed below.

In the synthetic route described above, the acylation is carried outwith an acylating agent, the identity of which is not critical; eitherthe difluoroalkanoyl halide:

or the difluoroalkanoic anhydride is suitable, although the latter isoften preferred. In general, the reaction is conducted by mixing theacylating agent and the substituted-3-nitro-2-aminopyridine. In the caseof a difluoroalkanoyl halide, the use of an acid accepting amide ororganic tertairy amine is preferred. Particularly suited organictertiary amines include triethylamine and pyridine; and suitable amidesinclude DMF and dimethylacetamide. The reaction goes forward attemperatures of from 25-100" C. and can be conducted in an inert liquidreaction medium, such as benzene; or an excess of the organic tertiaryamine can be employed as reaction medium; in addition, thedifiuoroalkanoic anhydrides are generally liquid, and an excess amountcan be used to assure fluidity. The reactiongoes forward readilyyielding the desired substituted-3-nitro-2-(2,2-difluoroalkanamido)pyridine product. Separation of the product, and, if desired,purification are carried out in conventional procedures.-

The reaction of the resulting substituted-3-nitro-2-(2,2-difluoroalkanamido) pyridine to prepare the ultimate products of thepresent invention, is in part the subject of copending application Ser.No. 21,226, filed Mar. 19, 1970. In general, it has been found thatsubjecting the substituted- 3-nitro-2-(2,2-difluoroalkanamido)pyridinecompounds,as well as other compounds, to any of a variety of reducingconditions results' the preparaiton of the ultimate substituted-IhydroXy-Z-tfl,1-difluoroalkyl)-1H imidazo(4,5-

the compounds. The first of these is as b)pyridine compounds of thepresent invention. It is believed that the reaction proceeds through anintermediate:

To date, it has not been possible to isolate this intermediate. As willbe obvious to those skilled in the art, however, the intermediate, ifisolatable from anysynthetic route, could itself be reacted to producethe compounds of the present invention.

While the reaction itself is unexpected, the reaction conditions are notcritical. As reducing agent, there can be employed, for example, any ofthe substances and conditions ordinarily employed for the reduction ofnitro compounds to amino compounds: hydrogen in the presence of acatalyst; zinc or iron in acid solution; sulfides in alkaline solution;hydrosulfite in alkaline solution; and the like. The reactions areconducted in accordance with the conditions known for each of theseagents (see Kirk-Othmer Encyclopedia of Chemical Technology, 2nd ed.,vol. 2, pages 76- 98 and references there cited [John Wiley and Sons,Inc., 1963, New York] and in all instances, cyclodehydration of theintermediate occurs spontaneously under such reducing conditions. 1

However, a preferred method for conducting the reduction reaction is theuse of hydrogen in the presenceof a catalyst. In general, in employingthis preferred method, the substituted-3-nitro-2-( 2,2difluoroalkanamido)pyridine, conveniently in an inert liquid as reactionmedium, is subjected to hydrogenation in the presence of catalyst,typically a noble metal and preferably palladium or platinum. Thecatalyst can be employed alone, or-especially in the instance ofpalladiumcan be supported on a carrier such as carbon or an alkali metalsalt. Conveniently, a Parr or other pressure apparatus is used tocontain the reaction mixture during hydrogenation, when conducted atsuperatmospheric pressures; however, the reaction also goes forward atatmospheric pressures. The reaction is further catalyzed by a smallamount of an acid, such as, for example, a mineral acid such ashydrochloric acid or a. compatible organic acid such as trifiuoroaceticacid.

The amounts of reactants employed are not critical. In general,preferred amounts are 2 moles of hydrogen per mole of the startingsubstituted-3 nitro-2-(2,2-difluoroalkanamido) pyridine and a catalyticamount of the noble metal, such as from 1 to 10 grams per kilogram ofthe starting compound. Temperatures of from 0 to 100 C. are operative,but better results are typically achieved at temperatures of from 10 to25 C.

When hydrogen uptake is complete, the product is separated from thereaction mixture in conventional procedures. Most typically, thereaction mixture is filtered to remove remaining catalyst, and thefiltrate evaporated to In an alternate synthetic route, a suitablysubstituted l-hydroxy compound of the present invention is itself usedas a starting material for the preparation of other of the compounds ofthe present invention. This synthetic route is particularly suited tothe preparation of the poly substituted compounds of the presentinvention (.n=2 or 3) where the necessary starting material for thefirst synthetic route is not readily available. The l-hydroxy compoundis subjected to reactions to introduce onto the pyridine ring one ormore desired groups and/or to convert one or more substituents alreadypresent on the pyridine ring to the desired group or groups.

Thus, for example, the l-hydroxy compound serving as starting materialfor this synthetic route can be halogenated or nitrated at a position orpositions previously unsubstituted. A nitrogroup already present can bereduced to an amino group; and an amino group already present can alsobe oxidized back to a nitro group. An amino group can also be diazotizedand replaced by, for example, a halo group, a nitrile group, or aloweralkylthio group. Oxidation of the loweralkylthio-substitutedcompound yields the corresponding loweralkylsulfonylsubstitutedcompound. The fiuorinated groups -CF Cl, or CF H) are readily obtained,initially by conversion of a nitrile to a carboxyl group; subsequenttreatment with SF, in the presence of HF yields the CF;, group.Alternately, conversion to an aldehyde and treatment with SF, aloneyields the CF H group; and subsequent chlorination converts the CF Hgroup to the corresponding -CF Cl group. An alkyl substituent isintroduced by reaction ofan alkyl lithium with a halosubstitutedl-hydroxy compound; and a perfluoroalkyl substituent is introduced byreaction of a halo-substituted l-hydroxy compound with a perfluoroalkyliodide in the presence of copper. This and numerous other conversion andsubstituent reactions are well known to those skilled in the art.Attention is directed to Fieser and Fieser, Advanced Organic Chemistry(Reinhold Publishing Corp., New York, N.Y., 1961), especially chapters 9and 17. See also Wagner and Zook, Synthetic Organic Chemistry (JohnWiley and Sons, Inc., New York, N.Y., 1953).

As will be understood by those skilled in the art, more than one of theforegoing reactions wil be needed to complete the preparation of some ofthe compounds of the present invention; and in the case of allreactions, due consideration must be given to the orienting effect ofsubstituent groups. Also, for those of the foregoing reactions whichutilize a nucleophilic reagent, it may be necessary that the l-hydroxygroup be converted to an ester or ether. Conversion is readily achievedby reacting the l-hydroxy compound with an alkyl halide or an acylhalide in the presence of a hydrogen chloride acceptor. The identity ofthe alkyl halide or acyl halide is not critical: suitable compoundsinclude the methyl halides and the acetyl halides. An ester derivativeis converted back to the l-hydroxy compound in conventional procedures.

The foregoing synthetic methods result in the preparation of the desiredsubstituted-l-hydroxy-2-(1,1-difluoroalkyl)-1H-imidazo(4,5-b) pyridinecompounds of the present invention. However, the proton of the OH groupbeing acidic, these compounds form salts with cations. Representativesuch salts include salts with alkali metals, such as sodium, potassium,lithium, cesium, and rubidium; alkaline earth metal salts, such ascalcium, strontium, and barium salts; and salts with organic amines.While the identity of the organic amine is not critical, preferredorganic amines are those which have relatively high base strength, suchas a dissociation constant (K of the order of 10 or greater. In general,the alkylamines, cycloalkylamines, alkylenepolyamines, and aralkylaminesare classes of compounds exhibiting adequate base strengths. Thus,representative bases include methylamine, dimethylamine, trimethylamine,methyldiethylamine, ethylamine, diethylamine, triethylarnine,n-propylamine di-npropylarnine, tri-n-propylamine, n-amylamine,cyclohexylamine, piperidine, pyrrolidine, N-methylpyrrolidine,diisopropylamine, ethylenediamine, tetramethylenediamine, ethanolamine,benzylamine, isobutylamine, di-n-butylamine, and the like. The foregoingsalts are prepared in conventional procedures, by reaction of the6-substitutedl-hydroxy 2 1,1-difluoroalkyl)imidazo (4,5-b) pyridine andthe particular amine or alkali metal or alkaline earth metal oxide,hydroxide, or salt. Such salt formation can be employed as a method offormulating the subject compounds.

The following examples illustrate the present invention and will enablethose skilled in the art to practice the same.

Example 1.5-chloro-3-nitro-2-(trifluoroaoetamido) pyridine5-chloro-3-nitro-2-aminopyridine (5.0 grams) and excess trifluoroaceticanhydride were refluxed together for 24 hours. TLC showed no reactionhad taken place. Pyridine (2.0 ml.) was then added. After fifteenminutes the solution solidified. The product was dissolved in chloroformand washed twice with water, and the chloroform was then evaporatedunder vacuum. The resulting product residue was recrystallized from amixture of benzene and aliphatic naphtha: M.P., 104-05 C., yield 6.0 g.

Analysis.Calcd.: C, 31.20; H, 1.12; N, 15.59. Found: C, 32.20; H, 1.44;N, 15.83.

Example 2.chloro-3-nitro-2-(trifluoroacetamido) pyridine The compound ofExample 1 was also synthesized by dissolving the S-chloro 3nitro-2-aminopyridine (5.0 grams) in a minimum amount of Warmtrifluoroacetic acid, and then adding 1.5 equivalents of trifluoroaceticanhydride and 0.5 milliliters of pyridine and refluxing for about anhour. The reaction mixture was then poured onto ice to precipitate the 5chloro-3-nitro-2-(trifluoroacetamido) pyridine compound, which wasseparated, dissolved in chloroform, and washed twice with water.Thereafter, the solution was shaken with activated carbon and filtered,and chloroform removed under vacuum to obtain a purified product. It wasfurther recrystallized from a low boiling (40-50 C.) petroleum ether,M.P. 104-05 C.

Example 3 .5- trifiuoromethyl) -3-nitro-2- (trifluoroacetamido) pyridine5-(trifiuoromethyl)-B-nitro 2 aminopyridine (2.0 grams) was mixed with10 milliliters of pyridine and 1 milliliter of trifluoroacetic anhydrideadded with cooling. After 30 minutes, the reaction mixture was heated toC. and maintained thereat for 10 minutes. The reaction mixture was thenpoured into ice and hydrochloric acid (of a concentration of 50 grams ofice per 10 milliliters of hydrochloric acid). The reaction mixture wasthen filtered and the resulting residue, the desiredS-(trifluoromethyl)-3-nitro 2 (trifluoroacetamido)pyridine, taken up inchloroform, dried, and solvent evaporated to obtain a purified product.It was further recrystallized from benzene, M.P., 68-70 C.

Example 4.5- (methylsulfonyl -3-nitro-2- (trifiuoroacetamido)pyridineS-(methylsulfonyl)-3-nitro 2 arninopyridine (2.0

. grams) was mixed with 15 milliliters of trifluoroacetic andissolved inchloroform, washed once with water, and dried over magnesium sulfate;the chloroform was then removed by evaporation, and the resultingproduct was recrystallized from benzene/acetone, M.P. 159-61 C.

Analysis.-Calcd.: C, 30.67; H, 1.93; N, 13.42. Found: C, 30.73; H, 2.00;N, 13.58.

Example 5.--1-hydroxy-2,6-bis (trifluoromethyl) lH-imidazo (4,5-b)pyridine -(trifluoromethyl)-3-nitro 2 aminopyridine (10.0 grams) intrifluoroacetic anhydride ml.) and pyridine (20 ml.) were heated in asteam bath for two hours. Solvents were then evaporated on a rotaryevaporator at 100 C. for one hour, and the residue was taken up in ethylacetate and hydrogenated over 2.0 g. of 5 percent palladium or carbon.The reaction mixture was then filtered, evaporated, and taken up inethanol; subsequently, the mixture was washed with 10 percenthydrochloric acid, dried over magnesium sulfate, and evaporated. Theresulting 1-hydroxy-2,6-bis(trifiuoromethyl) 1H imidazo(4,5-b)pyridineproduct was recrystallized from acetone, M.P., 239-40" C.

Analysis.-Calcd.: C, 35.44; H, 1.15; N, 15.50; F, 42.05. Found: C,35.40; H, 1.43; N, 15.28; F, 42.32.

Example 6.--6-chloro-1-hydroxy-2- (trifiuoromethyl)1Himidazo(4,5-b)pyridine S-chloro 3 nitro-2-(trifluoroacetamido)pyridine (2.0 grams) was hydrogenated with two moles of hydrogen inethanol containing 0.5 gram of 5 percent palladium on carbon. Theresulting reaction mixture was filtered and evaporated to separate thedesired -chloro-l-hydroxy-Z-(trifluoromethyl) 1H imidazo(4,5-b)pyridinecompound which, after recrystallization from benzene melted at 26870 C.

Analysis.Calcd.: C, 35.39"; H, 1.27; N, 17.69. Found: C, 35.59; H, 1.45;N, 17.77.

Example 7.6-chloro-l-hydroxy-Z-(trifiuoromethyl) imidazo(4,5-b)pyridineS-chloro 3 nitro-Z-(trifiuoroacetamido)pyridine (2.7 grams), anhydrousstannous chloride (3.8 grams), and 4.0 milliliters of concentratedhydrochloric acid were mixed in 20 milliliters of acetic acid. Themixture was cooled to temperatures of 0-1'0" C. and maintained thereatfor minutes. Water (50 milliliters) was then added to the reactionmixture, and the desireddchloro-l-hydroxy-Z-(trifluoromethyl)imidazo(4,5 b) pyridine productprecipitated. It was separated and dried. The yield was 1.3 grams, 55percent. The product so obtained melted at 264-66 C.

Example 8.-6-chloro-1-hydroxy-2-(trifiuoromethyl)-1Himidazo(4,5-b)pyridine triethylamine salt Example9.-+6-c'hloro-1-hydroxy-2 (trifiiiorometliyl)- lH-imidazo(4,5-b)pyridine benzylamine salt 6-chlor0 1hydroxy-Z-(trifluoromethyl)-1H-imidazo- (4,5-b)pyridine (1.4 grams) wasmixed w'ith lS milliliters of ethyl, acetate. The mixture was heated toreflux, and 0.6 milliliter of benzylamine was added dropwise. Themixture was then refluxed for another 30 minutes, cooled, and filtered,yielding the desired 6-chloro-1-hydroxy 2 (trifluoromethyD-lH-imidazo(4,5 b) pyridine benzylamine salt, M.P., 200 02. C. NMR analysis inhexadeuterodimethyl sulfoxide showed a peak at 236 c.p.s. (2H); a peakat 437 c.p.s. (5H); two meta-coupled doublets at the 462 c.p.s. (1H),the other at 500 c;f.p.s. (1H); and a broad peak at 474 c.p.s. (3H).

Analysis.-Calcd.: C, 48.75; H, 3.51; N, 16.25. Found: C, 48.52; H, 3.72;N, 16.07.

Example 10.-6-amino 1-hydroxy-2- (gtrifiuoromethyi)1H-imidazo(4,5-b)pyrid ine 2% ported in the following example. Examplell.5,7-dibrd ariiindl-hydroxy-Z-i(trifluoromethyl)-1H-1mid'azo(4,5-b)pyridine i} The aqueous solution of6-a'mino-1-hydroxy-2-(trifiuoromethyD-lH-imidazo(4,5-b) pyridineobtained as i reported in the preceding example was treated with2.2milliliters of bromine in an N -H O stream. Thereafter the reactionmixture was stirred for sixteen hours under nitrogen. The desired5,7-dibromo-6-aj mino-1-hydroxy-2- (triiluoromethyl 1H imidazo(4,5 b)pyridine precipitated in the reaction mixture and was separated byfiltration. It was taken up in 250 milliliters-jot diethyl ether,stirred for one hour, dried over magnesium sulfate, land filtered. Thediethyl ether was evaporated to git/e534 grams of the desired product inpurified form, M.P.;f 42- 4 C. (dec.).

Example 12.-5,7dibromo-6 itrd-l-hydroxy-ZZ- (trifiuoromethyl)-1H-imidazo4,5-b-)pyridine 5,7-dibromo 6 amino-l-hydroxy-Z-(trifiuorometliyl')-lH-imidazo(4,5-b)pyridine (25 milligrams) was added to a stirredsolution of 2 milliliters of 30 percent hydrogen peroxide and 5milliliters of sulfuric acid at about 5 C. The reaction mixture wasallowed to come to 25 C. Ejand permitted to stand for one hour. The:reaction mixture was then diluted with ice water, extracted withdief'jthyl ether, and dried over magnesium sulfate, and the etherevaporated leaving a residue, the-desired 5,7-dibrom'0-6- nitro 1hydroxy-Z-ftrifiuoromethyl)PIH-imidazo(f4,5- b)pyridine. It wasrecrystallized from chloroform, .M.P., 204 C. (dec.). i

Example 13.Diazonium salt derived: from 1,5 dihydroxy 7 bromo6-diazo-2-(,trifluoromethyD-lH-imidazo(4,5-b)pyridine 53 5,7-dibromo-6-amino 1hydroxy-2-(trifiuorometliyl)- lHimidazo(4,5-b)pyridine (112 grams) in 7milliliters of concentrated hydrochloric "acid was cooled with stirringto about 10 C. Sodium nitrite (10.35 gram) in i 2.0 milliliters of waterwas then added dropwise with stiri'ring and the reaction mixture wasstirred at; ambient tem iferature of about 25 C. for about sixteen andone-half hours. The reaction mixture: wasvthen jdiluted with water andfiltered toseparate 2;;S0lid, the desired diazoniumi salt derived from1,5-dihydrQxy-7=bronio;6 diazo-'2-(trifiubromethyl) lH-imidazo (4,5fb)pyridine. It; was promptly, analyzed by IR, which showed a peak art-2.80, confirming thel l stretch-and a low (1630-16 .40j1carbonylabsorption. The formula of this di az onidm salt is as folldws:

9 Example 14.-5,7-dibromo-6-chlorol-hydroxy-Z- (trifluoromethyl)-1H-imidazo (4, 5 -b pyridine 5,7- dibromo 6 amino 1 hydroxy 2(trifluoromethyl)-1H-imidazo(4,5-b)pyridine (1.2 grams) in 7 millilitersof concentrated HCl was cooled to -10 C. Thereafter, sodium nitrite(0.35 gram) was added as a solid. The addition was carried outportionwise to maintain the temperature below 10 C. Five minutes aftercompletion of the addition of the sodium nitrite, cuprous chloride (0.45gram) was added portionwise and the resulting reaction mixture stirredfor thirty minutes and filtered to separate the desired5,7-dibromo-6-chloro-l-hydroxy-2- (trifluoromethyl) 1H imidazo(4,5 b)pyridine product, M.P., 215 C.

Analysis.-Calcd.: C, 21.27; H, 0.25; N, 10.63. Found: C, 21.50; H, 0.50;N, 11.10.

Examples 15-47 Other products of the present invention are prepared inaccordance with the procedures and teachings hereinabove. Representativesuch other products include the following:

3,S-dinitro-Z-aminopyridine is reacted with difluoroacetic anhydride toobtain 3,5-dinitro-2-(difluoroacet amido)pyridine, which in turn ishydrogenated in the presence of platinum to obtain6-nitro-1-hydroxy-2-(difluoromethyl) -1H-imidazo (4,5-b pyridine.

-bromo-3-nitro-2-aminopyridine is treated with chlorodifluoroaceticanhydride to yield 5-bromo-3-nitro-2-(chlorodifluoroacetamido) pyridine,which on hydrogenation in the presence of palladium on barium sulfate,yields 6- bromo 1 hydroxy 2 (chlorodifiuoromethyl)-1H-imidazo(4,5-b)pyridine.

5-ethylsulfonyl-3-nitro-2-aminopyridine is reacted with trifiuoroaceticanhydride to obtain 5-ethylsulfonyl-3-nitro-2-(trifluoroacetamido)pyridine, which on hydrogenation in the presenceof palladium on carbon yields6-ethylsulfony11-hydroxy-2-(trifluoromethyl) 1H imidazo(4,5- b)pyridine.

5-chloro-3-nitro-2-aminopyridine is treated with pentafiuoropropionicanhydride to obtain 5-chloro-3-nitro-2-(pentafluoropropionamido)pyridine, which when hydrogenated in thepresence of palladium on carbon yields 6-chloro-l-hydroxy-Z-(pentafiuoroethyl) 1H imidazo(4,5- b)pyridine, M.P.240-42 C.

5-(chlorodifiuoromethyD-3-nitro-2-aminopyridine is reacted withheptafluorobutyric anhydride to obtain S-(chlorodifluoromethyl) 3 nitro2 (heptafluorobutyramido) pyridine, which on hydrogenation in thepresence of palladium on calcium sulfate yields 6-(chlorodifluoromethyl)l-hydroxy 2 (heptafluoropropyl) 1H imidazo(4,5-b) pyridine.

S-(n-butylsulfonyl)-3-nitro-2-aminopyridine is reacted withtrifluoroacetic anhydride to obtain S-(n-butylsulfonyl)-3-nitro 2(trifiuoroacetamido)py1idine, which on hydrogenation in the presence ofplatinum yields 6-(nbutylsulfonyl) 1 hydroxy 2 (trifluoromethyl-IH- imidazo (4,5 -b pyridine.

5-(difluoromethyl)-3-nitro-2-aminopyridine is reacted withdifiuoroacetic anhydride to obtain S-(difiuoromethyl) 3-nitro-2-(difluoroacetamido)pyridine, which when hydrogenated in the presence ofpalladium on barium sulfate yields 2,6-bis(difluoromethyl)-1-hydroxy 1Himidazo- (4,5-b)pyridine.

5-(methylsulfonyl)-3-nitro-2-aminopyridine is reacted withtrifluoroacetic anhydride to obtainS-(methylsulfonyl)-3-nitro-2-(trifluoroacetamido)pyridine which whenhydrogenated yields 6-(methylsulfonyl)-1-hydroxy-2-(trifluoromethyl) 1Himidazo(4,5-b) pyridine, M.P., 265- 68 C.

Analysis.Calcd.: C, 34.17; H, 2.15; N, 14.94. Found: C, 34.27; H, 2.37;N, 15.07.

S-chloro-3-nitro-2-aminopyridine is reacted with heptafiuorobutyricanhydride to obtain 5-chloro-3-nitro-2-(heptafluorobutyramido)pyridinewhich when hydrogenated yields 6-chloro 1 hydroxy 2(heptafluoro-n-propyl)- lH-irnidazo (4,5 -b pyridine.

S-chloro-3-nitro-2-aminopyridine is reacted with 2,2- difluoropropionicanhydride to obtain 5-chloro-3-nitro-2-(2,2-difluoropropionamido)pyridine, which on hydrogenation in thepresence of palladium on calcium sulfate yields6-chloro-1-hydroxy-2-(1,1-difluoroethyl) 1H imidazo- (4,5-b)pyridine.

S-(trifluoromethyl)-3-nitro-2-aminopyridine is reacted with2,2-difiuoro3-bromopropionic anhydride to obtain 5- (trifluoromethyl) 3nitro 2 (2,2-difluoro-3-bromopropionamido)pyridine, which onhydrogenation in the presence of platinum yields6-(trifiuoromethyl)-1-hydroxy 2 (1,1-difiuoro 2 bromoethyl) 1H imidazo-(4,5-b)pyridine.

S-iodo-3-nitro-2-aminopyridine is reacted with 2,2-difluorobutyricanhydride to obtain 5-iodo-3-nitro-2-(2,2- difluorobutyramido)pyridine,which when hydrogenated in the presence of palladium on barium sulfateyields 6- iodo 1 hydroxy 2(1,l-difluoro-n-propyl)-1H-imidazo(4,5-b)pyridine.

S-(methylsulfonyl)-3-nitro-2-aminopyridine is reacted with2,2-difluoro-3,4-dichlorobutyric anhydride to obtain5-(methylsulfonyD-3-nitro-2-(2,2-difluoro 3,4dichlorobutyramido)-pyridine which when hydrogenated yields 6-(methylsulfonyl) l hydroxy 2 (1,l-difiuoro2,3-dichloro-n-propyl)-lH-imidazo(4,5-b)pyridine.

5-fiuoro-3-nitro-2-aminopyridine is reacted with 2,2,3trifluoropropionic anhydride to obtain 5-fiuoro-3-nitro-2-(2,2,3-trifluoropropionamido)pyridine which on hydrogenation overpalladium on carbon yields 6-fluoro-1-hydroxy-2-( 1,1,2-trifiuoroethyl)-1H-imidazo 4,5 -b pyridine.

5(trifiuoromethyl)-3-nitro-2-aminopyridine is reacted with2,2-difluoro-4-iodobutyric anhydride to obtain S-(trifluoromethyl) 3nitro 2 (2,2-difluoro-4-iodobutyramido)pyridine, which on hydrogenationyields 6-(trifluoromethyl) l hydroxy 2 (1,1-difluoro-3-iodo-npropyl)--lH-imidazo (4,5-b pyridine.

5-chloro-3-nitro-2-aminopyridine is reacted with perfiuoroiictanoicanhydride to obtain 5-chloro-3-nitro-2- (2,2,3,3,4,4,5,5,6,6,7,7,8,8,8pentafluorooctanamido)pyridine, which on hydrogenation yields6-chloro-1-hydroxy- 2(perfluoro-n-heptyl) 1H imidazo(4,5-b)pyridine.This compound is reacted with dimethylamine to obtain the dimethylaminesalt thereof.

S-(trifiuoromethyl)-3-nitro-2-aminopyridine is reacted withperfiuorobutyryl chloride to yield S-(trifluoromethyl)-3-nitro 2(2,2,3,3,4,4,4-heptafiuorobutyramido)pyridine, which when hydrogenatedyields 6-(trifiuoromethy1)-1-hydroxy 2(perfluoro-n-propyl)-1H-imidazo(4,5- b)pyridine.

6-(chlorodifluoromethyl) 1 hydroxy 2(trifluoromethyl)-lH-imidazo(4,5-b)pyridine is reacted with pyridine toobtain the pyridine salt thereof.

6-(methylsu1fonyl)-1-hydroxy 2 (trifluoromethyl)-lH-imidazo(4,5-b)pyridine, in a dilute aqueous solution of sodiumhydroxide, forms the sodium salt thereof in solution.

6-nitro-l-hydroxy 2 (trifluoromethyl) 1H imidazo- (4,5-b)pyridine isreacted with an aqueous solution of calcium carbonate, yielding thecalcium salt thereof.

6-chloro-3-nitro-2-aminopyridine is reacted with trifluoroaceticanhydride to obtain 6-chloro-3-nitro-2-(trifiuoroacetamido)pyridine,which when hydrogenated yields S-chloro-l-hydroxy-Z- (trifluoromethyl)-1H-imidazo (4,5-b)pyridine, M.P. 216 C. (dec.).

Analysis.Calcd.: C, 35.39; H, 1.27; N, 17.69. Found:

C, 35.60; H, 1.48; N, 17.96.

4-chloro-3-nitro-2-aminopyridine is reacted with trifluoroaceticanhydride to obtain 4-chloro-3-nitro-2-(trifluoroacetamido)pyridine,which when hydrogenated 1 1 yields7-chloro-1-hydroxy-2-(trifluoromethyl)Jill-imidazo (4,5-b)pyridine,M.P., 170-1" C.

5 chloro-l-hydroxy-Z-(pentafluoroethyl)-1H-imidazo (4,5-b)pyridine isreacted with methanethiol to obtain 5 (methylthio) 1hydroxy-Z-(pentafluoroethyl)4H imidazo (4,5-b)pyridine which issubsequently oxidized to obtain the correspondingS-(methylsulfonyl)-1-hydroxy-2- (pentafiuoroethyl lH-imidazo (4,5-bpyridine.

7-chloro-l-hydroxy-2-(difiuoromethyl) 1H imidazo (4,5-b)pyridine isreacted with sodium fluoride to obtain 7-fiuoro 1 hydroxy 2(difluoromethyl)-1H-imidazo (4,5-b)pyridine, which is then converted toits calcium salt.

S-chloro-l-hydroxy 2 (l,1,2,2-tetrafluoroethyl)-1H- imidazo(4,5-b)pyridine is brominated to obtain S-chloro- 6 bromo 1hydroxy-2-(1,1,2,2-tetrafiuoroethyl)-1H- imidazo(4,5b)pyridine, which isthen converted to its sodium salt.

7 chloro 1 hydroxy-Z-(difiuorochloromethyl)-1H- imidazo(4,5-b)pyridineis reacted with ammonium hydroxide to obtain7-amino-l-hydroxy-Z-(difluorochloromethyl)-lH-imidazo(4,5-b)pyridinewhich is oxidized to the corresponding7-nitro-l-hydroxy-Z-(difluorochloromethyD-lH-imidazo (4,5-b)pyridine.Also, the 7-amino-1- hydroxy 2 (difiuorochloromethyl)-lH-imidazo(4,5-b)pyridine is treated with sodium nitrite and subsequently sodium cyanideto obtain the corresponding 7-cyano-1- hydroxy 2(difiuorochlorornethyl)-lH-imidazo(4,5-b) pyridine. On treatment with 70percent sulphuric acid the corresponding 7carboxy-l-hydroxy-2-(difluorochloromethyl)-1H-irnidazo(4,5-b)pyridine isprepared. On further treatment with SP and HF, there is obtained 7-trifiuoromethyl) l hydroxy-Z-(difluorochloromethyl)- lH-imidazo (4,5 -bpyridine.

fi-amino 1 hydroxy-Z-(trifiuoromethyl)-1I-l-imidazo (4,5-b)pyridine isnitrated to obtain 6-arnino-5,7-dinitrol-hydroxy-Z- (trifiuoromethyl) 1Himidazo (4,5-b)pyridine which is subsequently oxidized to obtain thecorresponding 5,6,7-trinitro-l-hydroxy-2-(trifluoromethyl)-lH-imidazo(4,5-b)pyridine.

-amino-1-hydroxy-2-(difiuoromethyl) 1H imidazo (4,5-b)pyridine ischlorinated to obtain6-amino-5,7-dichloro-l-bydroxy-Z-(difluoromethyl)-lH imidazo(4,5-b)pyridine. This compound is diazotized and treated with cuprous chlorideto convert it to 5,6,7-trichloro-1-hydroxy-2-( difluoromethyl)-1H-i-midazo 4,5 -b pyridine.

5,6-diamino 1 hydroxy 2 (trifiuoromethyDJH- imidazo(4,5-b)pyridine isdiazotized'and subsequently reacted with cuprous cyanide to obtain thecorresponding 5,6-dicyano 1 hydroxy-Z-(trifluoromethyl)-1H-imidazo(4,5-b)pyridine. It is converted to the corresponding 5,6- dicarboxycompound by treatment with 70 percent sulfuric acid. Subsequent reactionof the 5,6-dicarboxy-1- hydroxy-Z-(trifluoromethyl)-lH-imidazo(4,5b)pyridine with SF, in the presence of HF yields the corresponding2,5,6-tris(trifluoromethyl) 1 hydroxy-lH-imidazo(4,5- b)pyridine.Rosenmund reduction of the 5,6-bis-acid chloride gives the dialdehydewhich is reacted with SP to obtain 5,6bis(difluoromethyl)-1-hydroxy-2-(trifluoromethyl)-lH-imidazo(4,5-b)pyridine.In turn, this compound is chlorinated to obtain5,6-bis(difiuorochloromethyl) 1 hydroxy 2(trifluoromethyl)-lI-lI-imidazo (4,5-b)pyridine.

6-amino-5,7-dinitro-l-hydroxy 2 (trifluoromethyl)-1H-imidazo(4,5-b)pyridine is diazotized and the diazo group subsequentlyremoved entirely by reduction with hypophosphorus acid. The resulting5,7-dinitro-l-hydroxy-2-('trifluoromethyn-lH-imidazo(4,S-b)pyridine ishydrogenatedto the:' corresponding:"5,7-diamino-1-hydroxy-Z-(trifluoromethyl) 1H imidazo(4,5-b)pyridine.This compound is diazotized and subsequently reacted with the sodiumsalt of methyl mercaptan to obtain 5,7 bis(methylthio) 1 hydroxy 2(trifluoromethyl)-1H- imidazo(4,5-b)pyridine which is oxidized to thecorresponding 5,7-bis(methylsulfonyD-1-hydroxy-2-(trifiuoromethyl) 1H-imidazo (4,5 -b )pyridine.

5-chloro-3-nitro-2-aminopyridine is reacted with 2,2,3,3-tetrafluoropropionyl chloride to yield 5-chloro-3-nitro-2-(2,2,3,3-tetrafluoropropionamido)pyridine, which when hydrogenatedyields 6-chloro-l-hydroxy-Z-(-1;'1,2,2tetrafluoroethyl)-lH-imidazo(4,5-b)pyridine. This compound is reacted'With trimethylamine to prepare 6-chlorolhydroxy-Z-(l,1,2,2-tetrafiuoroethyl) 1H imidazo(4,5 b) pyridinetrimethylamine salt.

5-methyl-3-nitro-2-.aminopyridine is reacted with trifiuoroaceticanhydride to obtain 5-methyl:3-nit'ro2--,(trifiuoroacetamido)pyridine,which when hydrogenated yields 6 methyl- 1hydroxy-2-(trifluorornethyl)-1H- imidazo(4,5-b)pyridine, M.P., 3275 C...

S-(perfiuorodctyl)-3-nitro-2-aminopyridine is reacted with2,2,3,3-tetrafiuoropropionyl chloride to obtain 5- (perfluoroiictyl) 3nitro-2-(2,2,3,3-tetraiiuoropropionamido)pyridine, whichwhenhydrogenated yields 6-perfiuorooctyl) 1hydroxy'2-(l,1,2,2-tetrafluoroethyl)-1H- imidazo(4,5-b)pyridine.

The compounds of the present invention are adapted to be employed asherbicides. The compounds can be utilized to achieve broad herbicidalaction; hence, in its broadest sense, the present invention is directedto a method which comprises applying to aplant part, which can be astem, leaf, flower, fruit, root, or seed or other similar reproudctiveunit of a plant, a growth-inhibiting amount of one of thesubstituted-1-hydroxy-2-(1,1-difluoroalkyl)-lH-imidazo(4,5-b)pyridinecompounds of the present invention or one of the defined salts thereof.However, the compounds can also be utilized toi take advantage ofselective patterns of herbicidal activity;

It is not critical to the practice of the present invention thatcomplete destruction of undesirable vegetation be obtained, it beingadequate if the growth of the unwanted vegetation is merely inhibited.Especially where selective action is sought, inhibition falling short ofactual killing is adequate, particularly when combined with naturallyoccurring conditions such as limited moisture and the like which moreadversely alfect the vegetation selectively inhibited than the cropplant.

The compounds of the present invention are suited to a Wide variety ofherbicidal applications. Thus, for example, at rates which evoke theselective action of the compounds, which rates are defined morecompletely hereinbelow, the compounds can be, used as selectiveherbicides in crop plants, such as, for example, cotton, corn, sorghum,soybeans, and the like. In such use application can be made preemergentto both crops and weeds, or, preferably by means of a directed sprayapplication technique, postemergent to the crop plant but bothpreemergent and postemergent to the weedsfln another application, thecampounds can be used to give broad herbicidal action on noncrop land,including intermittently non-crop strips of contour-farmed land. Forsuch usage on so-called fallow land, application can be made in springto suppress vegetative growth until a fall or following spring planting,or in the fall to suppress vegetative growth until a spring or followingfall planting. Furthermore, in another application, the presentcompounds can .be utilized to control weeds in tree crop plantings, suchas plantings of the various citrus trees. In all of these variousapplications, and yet others for which the present compounds are suited,another advantage is that the compounds need not be disced into the soilbeing treated, it being adequate if one of the compounds, or aformulation containing one of the compounds, is merely spread onto thetop surface. I -fow- -ever, where desired or convenient, the compoundscan be disced into, or otherwise mechanically miiiedwith thes'oil.

In addition to the foregoing terrestrial embbdimentsgthe presentcompounds can also be utilized as aquatic herbicides.

The'practice of the present invention in any pins; numerous embodimentscan in some instances be carriedjbut with unmodified compound; however,for good resi ilts, it is generally necessary that the compound beempldyed in modified form, that is, as one component of a compositionformulated to implement the plant growth-inhibiting effects. Thus, forexample, the active agent can be mixed with water or other liquid orliquids, preferably aided by the usage of a surface active agent. Theactive agent can also be incorporated on a finely divided solid, whichcan be a surface active substance, to yield a wettable powder, which cansubsequently be dispersed in water or other liquid, or incorporated aspart of a dust which can be applied directly. Other methods offormulations are known in the art and can be employed in implementingthe present invention.

In carrying out the novel method of the present invention, the exactamount of the active agent employed is not critical and will vary,depending upon the type of growth-inhibiting effect desired, theidentity of the plants concerned, the particular active agent used,weather conditions, and the like. In general, a broad growth-inhibitingeffect is obtained with rates of from 0.5 to 20 pounds or more of activeagent per acre, and such rates are suitable and effective for control ofvegetative growth on fallow land. When it is desired to obtain aselective growthinhibiting effect on weeds in areas containing cropplants such as corn, soybeans, and cotton, rates of from 0.25 to poundsgenerally give good results. When in the typical mode of operation, theactive agent is employed as a composition comprising the agent, theexact concentration of active agent in the composition is not critical,except that the concentration and total amount of formulation employedbe adequate to supply the appropriate amount of active agent on a peracre basis. In general, good results are obtained when employingformulations containing the active agent in a concentration of from 0.5to percent or higher, in the instance of a liquid formulation; and in aconcentration of from 1.0 to 5.0 percent or higher, in the instance of adust, powder, granule, or the like. More concentrated formulations canbe prepared and are often preferred in that they can serve, dependingupon the particular application contemplated and the particularconcentration, both as a concentrated formulation for purposes ofshipment, storage, and the like, and as an ultimate treatingcomposition. Thus, for example, formulations often preferably contain asurface active agent and the present active agent, the latter beingpresent in an amount of from 0.5 to 99.5 percent, by weight; or aninert, finely divided solid and the present active agent, the latterbeing present in an amount of from 1.0 to 99.0 percent, by weight. Suchformulations, as indicated, can be employed directly in certainapplications, but can also be diluted and subsequently employed in manyother applications.

Liquid compositions containing the desired amount of active agent areprepared by dissolving the substance in a liquid, with or without theaid of a surface active dispersing agent such as an ionic or non-ionicemulsifying agent. Most preferably, the subject compound in acidic formis dissolved in a dilute aqueous solution of a base, such as, i.e.,sodium hydroxide, whereby a water soluble salt is prepared in solution.Although the use of an organic liquid carrier is seldom preferred inview of the foregoing, it can be used in conjunction with a surfaceactive dispersing agent. When so used, suitable such liquids includeagricultural spray oils and the petroleum distillates such as dieselfuel, kerosene, fuel oil naphthas and Stoddard solvent. The choice ofdispersing and emulsifying agent and the amount thereof employed isdictated by the nature of the composition and by the ability of theagent to facilitate the dispersion of the active agent in the carrier toproduce the desired composition. Dispersing and emulsifying agents whichcan be employed in the compositions include the condensation products ofalkylene oxides with phenols and organic acids, alkyl aryl sulfonates,polyoxyalkylene derivatives or sorbitan esters, complex ether alcohols,and the like. Representative surface active agents which are suitablyemployed in implementing the present invention are 14 identified in US.Pats. 3,095,299, second column, lines 25- 36, 2,655,447, column 5, and2,412,510, columns 4 and 5.

In the preparation of dust compositions, the active ingredient isintimately dispersed in and on a finely divided solid such as clay,talc, chalk, gypsum, limestone, vermiculite fines, perlite, and thelike. In one method of achieving such dispersion, the finely dividedcarrier is mechanically mixed or ground with the active agent.

Similarly, dust compositions containing the toxicant compounds can beprepared with various of the solid surface active dispersing agents suchas bentonite, fullers earth, attapulgite and other clays. Depending uponthe proportions of ingredients, these dust compositions can be employedas concentrates and subsequently diluted with additional solid surfaceactive dispersing agents or with chalk, talc, or gypsum and the like toobtain the desired amount of active ingredient in a composition adaptedto be employed for the suppression of the growth of the plants. Also,such dust compositions can be dispersed in water, with or without theaid of a dispersing agent, to form spray mixtures.

Formulations containing the present active agent are oftenadvantageously further modified by incorporation therein of an effectiveamount of a surfactant which facilitates the dispersion and spreading ofthe formulation on the plant leaf surfaces and the incorporation of theformulation by the plant.

In accordance with the present invention, the active agent can bedispersed in soil or other growth media in any convenient fashion.Applications can be carried out by simply mixing with the media, byapplying to the surface of soil and thereafter dragging or discing intothe soil to the desired depth, or by employing a liquid carrier toaccomplish the penetration and impregnation. The application of sprayand dust compositions to the surface of soil, or to plant parts or theabove ground surfaces of plants can be carried out by conventionalmethods, e.g., powder dusters, boom and hand sprayers and spray dusters,whether surface or air-borne. However, while such conventional modes ofapplication can be used, they are not required. As above noted, it is anadvantage of the present invention that the compounds serving as activeagent are active and effective as herbicides when merely placed on thesurface of the soil, without any additional step to assistincorporation. Thus, the compounds are of substantially the sameefiicacy regardless of whether they are applied to the surface only, orwhether they are applied to the surface and subsequently disced into thesoil.

In a further method, the distribution of the active agent in soil can beaccomplished by introducing the agent into the water employed toirrigate the soil. In such procedures, the amount of water is variedwith the porosity and water holding capacity of the soil to obtain adesired depth of distribution of the agent.

In addition, the present method also comprehends the employment of anaerosol composition containing one or more of the present active agentsas an active compound. Such a composition is prepared according toconventional methods wherein the agent is dispersed in a solvent, andthe resultant dispersion mixed with a propellant in liquid state. Suchvariables as the particular agent to be used and the nature of thevegetation which is to be treated will determine the desirability of thesolvent and concentration of the agent therein.

Example 48 6 chloro 1- hydroxy-2- (trifluoromethyl)-1H-imidazo(4,5-b)pyridine benzylamine salt was prepared as a means of formulation.More particularly, 1 gram of 6-chloro-1- hydroxy 2 (trifiuoromethyl) 1Himidazo(4,5-b)pyridine was suspended in about 10 milliliters of waterand 1 milliliter of benzylamine was added. The reaction mixture wasevaporated, yielding a syrup containing 6chloro- 1 hydroxy 2(trifluoromethyl) 1H imidaz0(4,5-b)

1 pyridine benzylamine salt. The syrup is useful to be diluted withwater to serve, when so diluted, as a spraying composition.

Examples 49-52 rating. Each compound evaluated was formulated as a sprayby one of the following procedures. In one method the particularcompound was wetted by grinding in a mortar with one part ofpolyoxyethylene sorbitan monolaurate. Five hundred parts of water wereadded slowly Various of the compounds to be employed as active 5 to theresultant creamy paste to give an aqueous disperagent in accordance withthe present invention were evalusion with a surfactant concentration of0.2 percent. This ated for preemergent application to various species ofdispersion was entirely satisfactory for spray application. plants. Inthis evaluation, a soil was prepared consisting In a second procedurethe compound wasidi'ssolved in of one part masonry sand and one partshredded top soil one volume of acetone, and the acetone solution wasblended together in a cement mixer. One gallon of this diluted withnineteen volumes of water containing Oll persoil was placed in a x cm.galvanized flat and Was cent of polyoxyethylene sorbitan monolaurate.patted down with a bench brush until level. A three-row In the followingtable setting forth the results of the marker was used to make 2 /2 cm.deep furrows in approxievaluation, column 1 gives the name of thecompound mately two-fifths of the flat Crop seeds consisting of four 15under test; column 2, the rate is pounds peracre'at which kernels ofcorn, five cotton seeds and five soybean seeds the compound was appliedto the test flat; and the remainwere placed in these furrows. A four-rowtemplate was ing columns, the injury tothe particular plant seeds orthen placed on the remaining soil and the indicated seedlings asmeasured bythe foregoing scalej'" TABLE 1 Injury Rating on prcemergenttreatment Lhs./ Fox- Velvet Compound acre Corn ta leaf6-ehloro-1-hydroxy-2-(trifiuoromethyl)-1H-imida 0( ,5-b) pyridine 2 3 :2

2,6-bis(trifluoromethyl)-1-hydroxy-lH-imldazo(4,5-b)pyridine 8 3 4fi-(methylsulfonyl)-1-hydroxy-2-(trifiuoromethy1)-1H-itnidazo(4,5-h)pyridine l 2 0 2 2b-chloro-l-hydroxy-2(trifiuoromethyl)-1H-imidaeo(4,5-b)pyridine V g a 211 Not tested at higher rate.

approximate numbers of each of the following seeds were planted, onespecies to each section: foxtail (millet), 80-100 seeds; velvetleaf(40-50 seeds); rough pigweed (150-250 seeds); and large crabgrass(100-150 seeds).

Sufiicient soil was added to cover the entire fiat. Thus, the weed seedswere covered to a depth of about 6 mm. and the crop seeds were coveredto a depth of about 3 cm.

Examples 53-58 Representative compounds of the present invention wereevaluated for postemergent application to plants-including corn andseveral weed species. The evaluation was carried out in accordance withthe procedures of Examples 49-52 except that the test solutions wereapplied about 9-12 days after the preparation and seeding of the Inassaying the effect of the composition as preemer- 40 flats. The resultsare as set forth in the following table.

TABLE 2 Injury rating on postemergenl: treatment:

LbsJ Orab- Pig- Compound acre Corn Cotton Soybean grass weed2,6-bis(trifiuoromethyl)-1-hydroxy-1H-imldazo(t,5-b)pyridlne i i tfi-methylsulfouyl-l-hydroxy-Z-(t-rifiuoromethyl-lH-hnidazo(4,5-b)pyrldine1 g g 'I-ehloro-1-hydroxy-2-trlfluoromethyl-lH-imidazo(4,5-b) pyridine ig fi-methyl-l-hydroxy-2-(trifluoromethyl)-1H-imidaao(4,5;b)pyridine 8 3l 3 1 5,7-dibromo-6-arnino-1-hydroxy-2-(trifiuoromethyD-lH-umdazo(4,5-b)pyridine. 8 3 3 5,7-dibromo-6-chloro-l-hydroxy-2-(trifiuoromethyl)-lH-imidazo (4,5-b) Pyndme-.- 8 4 4 1 Not tested at higher rates.

gent herbicides, a flat prepared as above, taken either on the day ofplanting or on the next day, was placed in a chamber equipped with aturntable and an air exhaust. The herbicidal composition, either aspray-type emulsion or a wettable powder, was applied to the flat with amodified DeVilbiss atomizer hooked to an air source. Twelve and one-halfmilliliters of the-composition under test were appliedto .each fiateither onthe-d'ay ofplanting or the succeeding day, Injury ratings-andpbservations as to type of injury were made eleven tofjtwelve daysafter treatment. The inj'ury rating scale used, as, as follows:

0no injury 1-slight injury 2-moderate injury I 3-severe injury 4deathWhen more than one determination was carried out at a given rate, anaverage value was calculated for the injury conditioning agents, and thelike.

Examples 59-60 6-chloro-l-hydroxy-2-(trifiuoromethyl 1H imdazo(4,-5-b)pyridine was evaluated in combination with 2-chloro4-ethy1amino-6-isopropylamino s -triazirre. and separately incombination with 2-chloro-2C6j-d thyl-N- (methoxymethyl)acetanilide forthe control of plants. The

evaluations were conducted as described in Examples 49- 52, except thatthe rates of compound diflered and the species were diiferent. Theresults were as set forth the methyD-Z-hydroxypyridine; The hydroxymoiety of this compound can be converted in standard procedures to anamino group, thus yieldingthe desiredS-(trifluoromethy1)-2-aminopyridine compound.

Preferred starting materials for utilization in the first syntheticroute are the mono-substituted 3-nitro-2-aminopyridines.

Those substituted-3-nitro-2-aminopyridine compounds wherein thesubstituent is alkylsulfonyl:

are prepared in accordance with the following reaction scheme: for thesake of simplicity, the scheme is shown for the preparation of aS-alkylsulfonyl compound, only.

The following example illustrates the preparation of the(alkylsulfonyl)-3-nitro-2-aminopyridine compounds.

Example 61. -(methylsulfonyl)-3-nitro-2- aminopyridine5-chloro-2-nitropyridine (8.0 grams) was added to a solution of 2.5grams of sodium methanethiolate in 100 milliliters of ethanol at atemperature of C. to which solution excess sodium methanethiolate wasadded portionwise. The resulting reaction mixture was then heated toreflux and refluxed for 15 hours with constant stirring. At the end ofthe 15 hours, the reaction mixture was filtered and allowed toconcentrate to 75 milliliters. The reaction mixture was then permittedto cool and filtered again, yielding the desired-(methylthio)-2-nitropyridine; it was recrystallized from ethanol, M.P.,l00.5-02.5 C.

To 3.4 grams of the 5-(methylthio)-2-nitropyridine in 50 milliliters ofglacial acetic acid there was added 23.8 grams of 30 percenthydrogenperoxide. ,The resulting reaction mixture was stirred for 60 hours at 25C., then poured over ice and filtered to separate the desired 5-(rnethylsulfonyl)-2-nitropyridine product, which, afterrecrystallization from ethanol/ acetone, melted at l65-7 C.

The entire yield of 5 (methylsulfonyl)-2-nitropyridine (3.2 grams) wasdissolved in about 100 milliliters of acetone and 1 teaspoon of Raneynickel slurry in ethanol added. The mixture was then shaken on a Parrhydrogenator for 15 hours at 60 p.s.i. Thereafter, the mixture wasfiltered and solvent evaporated, yielding the desired 5-(methylsulfonyl)-2-aminopyridine product. It'was mixed with hot watercontaining some charcoal, filtered and the S-(methylsulfonyl) 2aminopyridine (1.0 gram) was dissolved in milliliters of concentratedsulfuric acid and 2.0 milliliters of fuming nitric acid added dropwisewith stirring,,and the resulting reaction mixture stirred an additional10 minutes, warmed on a steam bath for, 10

, minutes, and allowed to stir at 25 C. for hours. The

" reaction mixture was then poured over ice with stirring."

mixture then cooled to 25 C. The resulting solid was crystallized frombenzene/acetone, M.P., 132-34 C.

Precipitation occurred, and the mixture was filtered vto sep-, arateS-(methylsulfonyl)-3-nitro 2 hydroxypyridine; it v was washed with waterand recrystallized from ethanol/ acetone, M.P., 229-32 C. a r

S-(methylsulfonyl) 3 nitro 2 hydroxypyridine (2.0 grams) was mixed with25 milliliters of thionyl chloride and 1 milliliter of dimethylformamideand the mixture refluxed for 2 hours. The reaction mixture was thenevaporated to separate 5-(methylsulfonyl)-3-nitro-2-chloropyridine. Itwas shaken with water to remove any traces of thionyl chloride, and thenfiltered and mixed with 50 milliliters of ammonium hydroxide. Thismixture was stirred, at room temperature, for 15 hours, then poured intoice water and filtered to separate 5-(methylsulfonyl)-3-nitro-2-aminopyridine. It was recrystallized from ethanol/acetone,M.P., 239-4l C.

Analysis.--Calcd.: C, 33.19; H, 3.25;-N,-19.35.-Found:-- C, 33.32; H,3.31;.N, 19.18.

In like manner are prepared the other (alkylsulfonyl)- 13-nitro-2-aminopyridine compounds:

6- (ethylsulfonyl) -3 -nitro-2-aminopyridine;

S- (isopropylsulfonyl -3 -nitro-2-aminopyridine;

4- n-propylsulfonyl )-3-nitro-2-aminopyridine;

5- (n-butylsulfonyl) -3-nitro-2-aminopyridine;

6- (isobutylsulfonyl) -3-nitro-2-aminopyridine;

5- (sec butylsulfonyl -3-nitro-2-aminopyridine; and 5-(terr-butylsulfonyl) -3-nitro-2-aminopyridine.

Intermediates in the preparation of these compounds include thefollowing:

6- (ethylthio -2-nitropyridine 5-(n-butylthio)-2-nitropyridine4-(n-propylsulfonyl)2-nitropyridine 5- (isobutylsulfonyl-2-aminopyridine 6-(isopropylsulfonyl)-3-nitro-2-hydroxypyridine 5-sec-butylsulfonyl -3-nitro-2-chloropyridine6-(ethylsulfonyl)-3-nitro-2-chloropyridine 5- (zert-butylsulfonyl-3-nitro-2-aminopyridine 6- (ethylsulfonyl -3 -nitro-2-aminopyridinePreferred compounds of the present invention are those mono-substitutedcompounds of the formula sms/ wherein R represents hydrogen, chlorine,fluorine, difiuoromethyl or trifluoromethyl, and R represents halogen,nitro, CF CF C1, 'CF H, or loweralkylsulfonyl of C -C Yet more preferredcompounds are those of the foregoing formula wherein the R suhstituentis located at the 6-position, i.e., compounds of the formula wherein Rand R are as above defined.

21 We claim: 1. A compound selected from the group consisting of thecompounds of the formula wherein R represents hydrogen, chlorine,fluorine, difluoromethyl, or trifluoromethyl, and R represents halogen,m'tro, CF -CF C1, CF H, or loweralkylsulfonyl of C -C and the alkalimetal salts thereof; the alkaline earth metal salts thereof; and thesalts thereof with organic amines having 2. K, of the order of 10- orgreater and selected from the group consisting of methylamine,dimethylamine, trimethylamine, methyldiethylamine, ethylamine,diethylamine, triethylamine, n-propylamine, di-n-propylamine,tri-n-propylamine, n-amylamine, cyclohexylamine, piperidine,pyrrolidine, N-methylpyrrolidine, diisopropylamine, ethylenediamine,tetramethylenediamine, ethanolamine, benzylamine, isobutylamine, anddi-n-butylamine.

2. The compound of claim 1 which is6-chloro-1-hydroxy-Z-(trifluoromethyl)-1H-imidazo(4,5-b)pyridine.

3. The compound of claim 1 which is 2,6-bis(trifluoromethyl)-1-hydroxy-1H-imidazo(4,'5-b) pyridine.

4. The compound of claim 1 which is6-(methylsulfonyl)-l-hydroxy-Z-(trifluoromethyl) 1H imidazo(4,5-b)pyridine.

5. The compound of claim 1 which is fi-nitro-l-hydroxy-2-(trifluoromethyl)-1H-imidazo(4,5-b)pyridine.

6. The compound of claim 1 which isS-chloro-l-hydroxy-2-(trifluoromethyl)-1H-imidazo(4,5-b)pyridine.

7. The compound of claim 1 which is6-chloro-1-hydroxy-2-(1,1,2,2-tetrafiuoroethyl) 1H imidazo(4,S-b)pyridine.

8. The compound of claim 1 which is6-chloro-1-hydroxy-Z-pentafiuoroethyl-lH-imidazo (4,5 -b) pyridine.

References Cited Roberts et al., Basic Principles in Organic Chemistry,Benjamin Publishers, p. 806, 1965.

ALAN L. ROTMAN, Primary Examiner US. Cl. X.R.

260-270 R, 293.7, 294.8 C, 295 AM; 71--92

